Summary The frequently quoted figure for the fractional univalent reduction of oxygen to superoxide in mitochondria is certainly too high by at least one order of magnitude. This is so because the higher number (2%) was derived from mitochondria whose cytochrome c oxidase was blocked with cyanide. Nevertheless, even the more correct number (0.1%) means that the production of and H2O2 in mitochondria is large and apt to result in damage to macromolecules in spite of such defensive enzymes as superoxide dismutases and glutathione peroxidase. The data available for nematodes and flies provide a compelling case for the view that the accumulation of oxidative damage to specific mitochondrial proteins leads to the progressive dysfunction that we see as senescence. The data available from work with mammals are much weaker and do not yet allow a strong position to be taken.
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